Cost-effectiveness of fractional exhaled nitric oxide (FeNO) measurement in predicting response to omalizumab in asthma.

Purpose: To use a modeled analysis to examine the cost-effectiveness of utilizing fractional exhaled nitric oxide (FeNO) as a biomarker to aid in the identification of omalizumab responders in patients with moderate-to-severe allergic asthma. Omalizumab is a biological drug used to treat asthma in adults and children 12 years and older. Patients and methods: We conducted a decision analysis in which two alternative strategies for predicting omalizumab response were assessed: 1) testing response via a 12-week trial of omalizumab and 2) using FeNO measurement to screen patients for likely omalizumab response prior to initiating a 12-week trial of omalizumab. In the standard of care arm, trial omalizumab responders continue on to receive 12 months of continuous omalizumab therapy. In the FeNO measurement predictor arm, patients with FeNO measurements >19.5 ppb are started on a trial of omalizumab. Trial omalizumab responders in this arm are then also tracked for 12 months of continuous omalizumab therapy. Results: Per-patient costs during the trial and initial treatment periods total $10,943 for FeNO + omalizumab and $13,703 for omalizumab only. The expected cost per responder during the trial period is $4,326 for FeNO + omalizumab and $7,786 for omalizumab only. Conclusion: Use of FeNO measurement to identify omalizumab responders decreases the expected per-patient cost by nearly 50% during the trial period and continues to show cost savings through the initial treatment period of 12 months. Our analysis may serve as a model for policy and clinical practice regarding the use of FeNO to determine omalizumab response and has widespread implications for health care payers, who may choose to require FeNO measurement and prespecify a minimum FeNO value to determine patient eligibility for omalizumab trial.

Cost impact of monitoring exhaled nitric oxide in asthma management.

BACKGROUND: Asthma guidelines recommend periodic assessment of impairment and risk factors to prevent exacerbations, which can lead to hospitalization and increased health care utilization and cost. According to recent meta-analysis data, fractional exhaled nitric oxide (FeNO) monitoring is associated with a 40-50% reduction in the risk of exacerbations. OBJECTIVE: Cost modeling of these data indicates the potential for significant cost savings with FeNO use. Therefore, we attempted to verify this potential for cost savings within a real-world data base of Medicare beneficiaries. METHODS: This retrospective observational study investigated asthma-related claims from a Medicare data base. Beneficiaries were included who had 2 years of records after an asthma-related inpatient hospitalization (IP) or emergency department (ED) claim. A case-crossover analysis was completed of asthma-related IP or ED events before and after FeNO use during the 2-year study period. RESULTS: Of the 5911 asthma beneficiaries who met the inclusion criteria within the data base, 101 had an FeNO test during the 2-year study period. During the period before FeNO use, 98 of 101 (97%) beneficiaries had an asthma-related IP or ED event compared with 46 of 101 (46%) during the FeNO period. Asthma-related IP or ED claims and charges per beneficiary per day during the period before FeNO were 0.004 and $16.21 compared with 0.002 and $6.46 during the FeNO period (p = 0.0433 and p = 0.0133, respectively). CONCLUSION: FeNO monitoring in beneficiaries with a history of exacerbations was associated with a substantial reduction in asthma-related IP and ED claims and charges. These data supported cost modeling estimates and demonstrated that FeNO use in asthma management was associated with significant cost savings.

A Review of the Utility and Cost Effectiveness of Monitoring Fractional Exhaled Nitric Oxide (FeNO) in Asthma Management.

Asthma is a common chronic respiratory disease affecting nearly 8% of the U.S. POPULATION: It results in substantially higher direct and indirect costs as well as an increased mortality risk and poorer quality of life, particularly among patients with difficult-to-control asthma. While several physiologic tests, including spirometry, are typically used to diagnose and characterize asthma, they do not provide the sensitivity and specificity required to accurately reflect the underlying heterogeneous inflammatory pathways. Fractional exhaled nitric oxide (FeNO) is a validated, noninvasive biomarker for T2-driven (i.e., allergic) airway inflammation that correlates with sputum eosinophils at or greater than 3% across various asthma phenotypes. Its use as a biomarker in asthma is well supported by numerous peer-reviewed articles and guidelines. There is also evidence that its use in clinical settings for patients with uncontrolled asthma is cost effective, given its ability to improve the accurate diagnosis of asthma, monitor treatment response, optimize inhaled corticosteroid dosing, and identify patient nonadherence. It may also have a role in identifying patients who are possible candidates for treatment with biologics.

Cost-Effectiveness Analysis of Monitoring Fractional Exhaled Nitric Oxide (FeNO) in the Management of Asthma.

PURPOSE: Current asthma guidelines combine treatment, follow-up, and reevaluation to manage asthma control, reduce impairment, and decrease risk of morbidity in patients. Clinical use of biomarkers, such as fractional exhaled nitric oxide (FeNO), along with standard management can provide clinicians with improved ability to recognize airway inflammation, optimize drug therapy, and potentially increase asthma control. Our objective is to examine the impact of FeNO monitoring on the cost effectiveness of asthma management compared with management without FeNO. Sensitivity analyses further examine the impact of FeNO monitoring on patients with varying levels of severity and exacerbations. DESIGN AND METHODS: A decision-tree analysis of estimated outcomes and costs associated with annual management of asthma was utilized to simulate asthma management and treatment cost scenarios, comparing estimated 12-month costs and outcomes using the following treatment alternatives: (1) current standard of care (SOC) or (2) FeNO utilized in conjunction with the current SOC. Costs were estimated from the perspective of the health care payer; cost effectiveness was estimated as cost per quality-adjusted life year (QALY). RESULTS: FeNO in conjunction with SOC guidelines has decreased expected per-patient annual expenditure ($2,228) and increased expected per-patient annual QALYs (0.844) compared with SOC alone ($2,637 and 0.767). FeNO monitoring with SOC resulted in decreased annual costs and increased annual QALYs compared with SOC alone, and this difference was consistent through all one-way sensitivity analyses. CONCLUSION: Our analysis revealed that FeNO monitoring to guide asthma management is cost effective and could result in increased QALYs and decreased health care costs associated with asthma management.

Measurement of fractional exhaled nitric oxide in real-world clinical practice alters asthma treatment decisions.

BACKGROUND: Assessment of asthma using clinical measures alone often fails to detect underlying airway inflammation. Fractional exhaled nitric oxide (FeNO) is a recognized biomarker of type 2 airway inflammation in asthma. Measurement of FeNO is instrumental in the assessment and management of patients with corticosteroid-sensitive asthma. OBJECTIVE: To determine the impact of measuring FeNO on asthma management in real-world clinical practices. METHODS: Clinicians from 337 US practices performed a clinical assessment and recorded treatment plans before and after measuring FeNO in 7,901 patients with asthma. Airway inflammation was classified as low, intermediate, or high according to the clinician's usual procedures, including clinical examination, spirometry, and symptoms. Clinicians recorded asthma medication plans, indicating medications to be initiated, continued, or stopped. FeNO measurement was performed, followed by documentation of any change(s) in the treatment plans based on the FeNO value (eg, initiating new medications or changing the dose of or discontinuing existing medications). RESULTS: Clinical assessment was concordant with FeNO measurement in only 56% of cases, matching FeNO more frequently in patients with low inflammation (64%) vs high inflammation (34%). After FeNO measurement, clinicians modified their treatment plan in 31% and altered prescriptions for inhaled corticosteroids in 90% of cases. Inhaled corticosteroids were initiated or their dose increased in 66% of patients with high inflammation but discontinued or their dose decreased in only 9% of patients with low inflammation. CONCLUSION: Measurement of FeNO enabled clinicians to assess underlying airway inflammation, leading to a significant revision of their treatment plans compared with real-world clinical assessment of asthma alone.

Effectiveness of omalizumab in reducing corticosteroid burden in patients with moderate to severe persistent allergic asthma.

BACKGROUND: Asthma guidelines advocate maintaining asthma control while minimizing corticosteroid exposure. OBJECTIVE: To assess the reduction in corticosteroid burden during long-term treatment and the corresponding impact of this reduction on asthma control, lung function, and inflammation in patients with moderate to severe allergic asthma. METHODS: We conducted a pooled analysis (N = 1,071) of 2 similarly designed, randomized, double-blind, placebo-controlled omalizumab trials and their extension phases. Each study included a 16-week steroid-stable phase, a 12-week steroid-reduction phase, and a 24-week extension phase. Patients received subcutaneous omalizumab (minimum, 0.016 mg/kg/IU (IgE/mL) every 4 weeks) or placebo every 2 or 4 weeks. Outcomes included change from baseline in inhaled corticosteroid dose, number of oral corticosteroid bursts, and other clinical measures, including asthma exacerbations and change in asthma quality-of-life score (questionnaire), lung function, and eosinophil count. RESULTS: The median reduction from baseline in inhaled corticosteroid dose (beclomethasone dipropionate equivalent dose) by the completion of the extension phase was greater for the omalizumab group than for the placebo group (-420.0 vs -252.0 µg/d; P < .001). During that time, omalizumab-treated patients required fewer oral corticosteroid bursts overall for treatment of acute exacerbations (mean, 0.2 vs 0.3; relative risk, 0.56; 95% confidence interval, 0.41 to 0.76; P < .001) and demonstrated greater improvements in measures of asthma control. CONCLUSION: The addition of omalizumab to baseline therapy in patients 12 years or older with moderate to severe persistent allergic asthma resulted in a durable reduction in the overall steroid burden and improvement in other clinical measures of asthma control.

Effect of pretreatment with omalizumab on the tolerability of specific immunotherapy in allergic asthma.

BACKGROUND: Although specific immunotherapy is a valuable treatment option for patients with allergic asthma, the potential for systemic allergic reactions has limited its use, especially for patients with symptomatic disease. OBJECTIVE: To evaluate omalizumab's effect on the tolerability of specific immunotherapy in patients with symptomatic persistent asthma not adequately controlled with inhaled corticosteroids. METHODS: This multicenter, double-blind, parallel-group study randomized patients to treatment with omalizumab or placebo, after which they received specific immunotherapy to at least 1 of 3 perennial aeroallergens (cat, dog, and house dust mite) according to a 4-week, 18-injection cluster regimen, followed by 7 weeks of maintenance therapy. The primary efficacy variable, a systemic allergic reaction after immunotherapy, was analyzed by using the Cochrane-Mantel-Haenszel test. RESULTS: A total of 248 randomized patients (126 omalizumab, 122 placebo) received at least 1 dose of immunotherapy and were evaluated for efficacy. Patients receiving omalizumab experienced significantly fewer systemic allergic reactions to immunotherapy than those receiving placebo (17/126 [13.5%] vs 32/122 [26.2%]; P = .017; 95% CI, 2.91% to 22.56%) and had fewer respiratory-related (grade 3) systemic allergic reactions (6 vs 24, respectively). Grade 4 reactions were reported in 2 patients in each group. More omalizumab patients were able to reach the target maintenance immunotherapy dose (110 [87.3%] vs 88 [72.1%], respectively; P = .004). CONCLUSION: Use of omalizumab in patients whose asthma was symptomatic despite use of inhaled corticosteroids was associated with fewer systemic allergic reactions to specific immunotherapy and enabled more patients to achieve the target immunotherapy maintenance dose.

Recent asthma exacerbations predict future exacerbations in children with severe or difficult-to-treat asthma.

BACKGROUND: Children with severe/difficult-to-treat asthma experience high morbidity including frequent severe exacerbations. More knowledge is required to identify predictors of these exacerbations to reduce their occurrence. OBJECTIVE: To investigate the risk of future severe exacerbations (FSEs) in children with severe/difficult-to-treat asthma and recent severe exacerbations (RSEs). METHODS: We analyzed the occurrence and association of RSE (defined as 1 or more corticosteroid bursts during the 3 months before each of 3 annual visits) and FSE (defined as 1 or more corticosteroid bursts 6 or 12 months later) in children age 6 to 11 years in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens 3-year observational study. Repeated measures logistic regression analysis assessed the risk of FSE adjusted for demographics and clinical variables. RESULTS: In a multivariable model, FSE at 6 months was most strongly predicted by RSE (odds ratio [OR], 3.08; 95% CI, 2.21-4.28) and having 3 to 4 allergic triggers (OR, 2.05; 95% CI, 1.31-3.20). Race (OR, 1.77; 95% CI, 1.25-2.51) and being very poorly controlled according to the impairment component of the National Heart, Lung, and Blood Institute guidelines (OR, 1.59; 95% CI, 1.14-2.23) also significantly predicted FSE. CONCLUSION: Recent severe asthma exacerbations are an important independent predictor of FSE in children with severe/difficult-to-treat asthma and should be considered when establishing asthma management plans.

Efficacy of omalizumab in cat-allergic patients with moderate-to-severe persistent asthma.

Cat allergen (Fel d 1) is a pervasive and common trigger of exacerbations in sensitized patients with IgE-mediated asthma. This study was designed to evaluate the effect on asthma-related outcome measures of adding omalizumab to current treatment in patients with moderate-to-severe persistent asthma and cat allergen sensitivity. A pooled analysis was conducted of two double-blind, placebo-controlled, 28-week pivotal U.S. registration trials. In all patients, asthma was inadequately controlled with moderate-high dose inhaled corticosteroids. Patients were randomized to receive subcutaneous omalizumab (minimum, 0.016 mg/kg per IgE IU/mL every 4 weeks) or matched placebo. The effects of omalizumab on asthma-related outcomes were assessed for patients with cat allergen sensitivity (n = 811), identified by positive skin-prick test. The mean number of asthma exacerbations requiring treatment with systemic steroid bursts in cat allergen-sensitive patients was lower in those receiving omalizumab versus placebo (0.6 versus 1.3, respectively; relative risk = 0.50, p < 0.001). Compared with placebo, omalizumab treatment led to significantly lower asthma symptom scores (least squares means (LSMs) treatment difference [95% confidence interval {CI}]: -0.57 [-0.77, -0.37]; p < 0.001), less rescue medication use (LSMs treatment difference [95% CI]: -0.75 puffs of rescue beta-agonist per day [-1.04, -0.46]; p < 0.001), and improvement in forced expiratory volume in 1 second (LSMs treatment difference [95% CI]: 100.84 mL [51.86, 149.81]; p < 0.001). Patient and investigator global evaluations of treatment effectiveness paralleled these outcomes. Omalizumab improved asthma control by reducing exacerbations and decreasing symptoms in cat-allergic patients with moderate-to-severe persistent IgE-mediated asthma.

A retrospective randomized study of asthma control in the US: results of the CHARIOT study.

BACKGROUND: The third version of the National Asthma Education and Prevention Program (NAEPP) Expert Panel Report (EPR-3): Guidelines on the Diagnosis and Management of Asthma emphasizes the need to use asthma control rather than patient severity to base adjustments to treatment and ultimately improve patient outcomes. The objectives of the current study were to assess control of patients with moderate-to-severe asthma, examine the natural history of the disease, practice patterns and resource utilization in specialty community practices according to recently reviewed NAEPP guidelines. RESEARCH DESIGN AND METHODS: This analysis represents a retrospective, multicenter, randomized study of 1009 patient charts in sixty United States allergy and pulmonary medicine community practices. The proportion of patients with controlled and uncontrolled asthma over 12 months, prevalence and characteristics of atopy, past asthma history, pulmonary function, medications and treatment patterns, patient and clinical practice characteristics were analyzed. MAIN OUTCOME MEASURES: The primary outcome of interest was asthma control. RESULTS: A total of 365 male and 644 female patients with moderate-to-severe persistent asthma (mean 43.2 +/- 17.1 years) were enrolled. 81.9% of patients were uncontrolled according to recent NAEPP guidelines. Importantly, a greater percentage of patients with moderate asthma vs. severe persistent asthma were uncontrolled (p < 0.0114). Atopy was detected in 92% of patients. Patients with early onset of asthma were associated with control (p < 0.0433). Atopic symptoms, such as allergic rhinitis (p < 0.0130) and rhinosinusitis (p < 0.0476), were associated with uncontrolled asthma. Uncontrolled patients were also associated with more medications (a mean of 4.05 +/- 1.87 medications) than were controlled patients (a mean of 3.40 +/- 1.37 medications (p < 0.0001), although the temporal relationship of this association was not recorded. Limitations may have included patient and/or study site selection bias and difficulty in the process of operationalizing the definitions of control and disease severity. Since the current study only examined patients from specialty practices, the results may not be generalizable to the overall asthma population. CONCLUSIONS: Greater than 80% of asthma patients from specialty practices were uncontrolled with regard to asthma symptoms. Atopic symptoms, such as allergic rhinitis and rhinosinusitis, in addition to a greater number of medications, were associated with uncontrolled asthma. Moreover, patients designated as having asthma of moderate severity were associated with being uncontrolled more than were those with severe asthma (p < 0.0114), which suggests that the former population may not have received adequate assessment of impairment or risk, with subsequent changes in treatment for control of symptoms.

Effect of omalizumab on the need for rescue systemic corticosteroid treatment in patients with moderate-to-severe persistent IgE-mediated allergic asthma: a pooled analysis.

BACKGROUND: Allergic asthma is an immunoglobulin E (IgE)-mediated disease characterized by frequent exacerbations following exposure to relevant allergens that leads to the development of chronic airway inflammation. Omalizumab, an anti-IgE antibody, reduces asthma exacerbation and hospitalization rates in patients with IgE-mediated allergic asthma. We investigated the effect of omalizumab on asthma outcomes in a retrospective pooled analysis of data from phase III clinical trials in patients (>or= 12 years) with moderate-to-severe persistent IgE-mediated allergic asthma. METHODS: Systemic corticosteroid bursts and physician and patient overall assessments of asthma control were assessed in patients who received add-on omalizumab or current asthma therapy (control). The association of physician and patient overall assessments with the number of steroid bursts were also evaluated. RESULTS: The analysis encompassed 4308 patients with moderate-to-severe persistent IgE-mediated allergic asthma (93% met GINA 2002 criteria for severe persistent asthma) from seven clinical trials. The number of systemic corticosteroid bursts was significantly lower in omalizumab-treated patients than in the control group (relative risk [95% CI]: 0.57 [0.48-0.66], p < 0.001). In addition, 58.5% of omalizumab recipients had complete/marked improvement in asthma control according to the physician's overall assessment (responders) vs. 36.9% in the control group (p < 0.001). Similarly, 64.2% of omalizumab patients vs. 43.9% of control patients had complete/marked improvement according to the patient's overall assessment (p < 0.001). There were statistically significant associations between systemic corticosteroid bursts and physician (Goodman-Kruskal gamma [95% CI]: 0.32 [0.26-0.38]) and patient (gamma [95% CI]: 0.29 [0.23-0.36]) overall assessments. This pooled analysis has limitations as it was not pre-specified. CONCLUSIONS: Omalizumab therapy reduced the need for systemic corticosteroid bursts and improved effectiveness of asthma treatment as judged by both physicians and patients.